Effects of some persistent halogenated environmental contaminants on aromatase (CYP19) activity in the human choriocarcinoma cell line JEG-3.
Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB126), a technical PCB mixture (Aroclor 1016), and a technical toxaphene mixture (Camphechlor) on aromatase (CYP19) activity were investigated in human choriocarcinoma JEG-3 cells. After 18 h incubation with TCDD, PCB126, Aroclor 1016 or toxaphene, ethoxyresorufin-O-deethylase (EROD), and aromatase activity were determined. To exclude serum effects, incubations were carried out with or without fetal calf serum in the medium. EROD activity was induced by both TCDD and PCB126 in the presence or absence of serum, which indicates that JEG-3 cells are responsive toward dioxin-like chemicals. Neither Aroclor 1016 nor toxaphene affected EROD activity in these cells. Calculated EC50 values for induction of EROD activity were 0.71 and 0.40 nM for TCDD, and 48 and 20 nM for PCB126 in presence or absence of serum, respectively. Incubation with TCDD or PCB126 with or without serum caused a concentration-dependent decrease in the aromatase activity of up to 4.9-fold. Calculated EC50 values for this effect were 52 pM and 13 nM for TCDD, and 75 and 48 nM for PCB126 in the presence and absence of serum, respectively. Aroclor 1016 and toxaphene had no effect on aromatase activity at concentrations up to 1.0 microM for Aroclor 1016 or 3.0 microM for toxaphene. These results show that aromatase activity can be decreased in a concentration dependent way within the same range where EROD activity is increased. In view of these results, possible effects of dioxin-like compounds on estrogen producing and androgen target cells should be studied in more detail.
Drenth
H J
HJ
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Bouwman
C A
CA
Seinen
W
W
Van den Berg
M
M
D001140:Aroclors / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D002822:Choriocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology*; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D014112:Toxaphene / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D001140:Aroclors; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; C027386:Aroclor 1016; D014112:Toxaphene; D011078:Polychlorinated Biphenyls; D001141:Aromatase; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl